Trial Outcomes & Findings for A Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease Dementia (NCT NCT02972658)

NCT ID: NCT02972658

Last Updated: 2019-12-03

Results Overview

ADAS-Cog13 (13-item version of ADAS-Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment\*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, apolipoprotein E4 (APOE4) status, acetylcholinesterase inhibitor (AChEI) use at baseline, age at baseline, and pooled country.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 421 participants
• Primary outcome timeframe: AZES Baseline through AZFD Week 26
• Results posted on: 2019-12-03

Participant Flow

Participants who completed feeder study [AZES (NCT02245737)] were enrolled in this study.

Participants who were randomized in Study AZES to either 20 milligrams (mg) or 50 mg of lanabecestat continued on the treatment allocation from the feeder study. Participants randomized to placebo in Study AZES were randomized in a blinded fashion, 1:1 ratio, to either lanabecestat 20 mg or 50 mg daily (QD), administered orally.

Participant milestones

Measure	AZES Placebo/AZFD Lanabecestat 20 mg Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	AZES Placebo/AZFD Lanabecestat 50 mg Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.
Overall Study STARTED	76	139	75	131
Overall Study Received at Least 1 Dose of Study Drug	76	139	74	131
Overall Study COMPLETED	0	1	0	0
Overall Study NOT COMPLETED	76	138	75	131

Reasons for withdrawal

Measure	AZES Placebo/AZFD Lanabecestat 20 mg Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	AZES Placebo/AZFD Lanabecestat 50 mg Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.
Overall Study Adverse Event	0	3	0	2
Overall Study Other-determined by Investigator	1	1	0	0
Overall Study Death	0	0	0	1
Overall Study Lost to Follow-up	0	1	1	2
Overall Study Progressive Disease	0	1	0	1
Overall Study Withdrawal by Subject	4	4	1	6
Overall Study Withdrawal due to Caregiver Circumstance	1	1	1	0
Overall Study Sponsor Decision	70	127	72	119

Baseline Characteristics

A Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease Dementia

Baseline characteristics by cohort

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 Participants Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=139 Participants Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	AZES Placebo/AZFD Lanabecestat 50 mg n=75 Participants Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=131 Participants Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.	Total n=421 Participants Total of all reporting groups
Age, Continuous	70.7 Years STANDARD_DEVIATION 6.6 • n=5 Participants	69.8 Years STANDARD_DEVIATION 7.8 • n=7 Participants	71.1 Years STANDARD_DEVIATION 6.6 • n=5 Participants	70.1 Years STANDARD_DEVIATION 6.7 • n=4 Participants	70.3 Years STANDARD_DEVIATION 7.0 • n=21 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	76 Participants n=7 Participants	40 Participants n=5 Participants	75 Participants n=4 Participants	226 Participants n=21 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	63 Participants n=7 Participants	35 Participants n=5 Participants	56 Participants n=4 Participants	195 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	62 Participants n=5 Participants	115 Participants n=7 Participants	54 Participants n=5 Participants	114 Participants n=4 Participants	345 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	20 Participants n=7 Participants	17 Participants n=5 Participants	14 Participants n=4 Participants	58 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	23 Participants n=7 Participants	10 Participants n=5 Participants	16 Participants n=4 Participants	56 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants	104 Participants n=7 Participants	51 Participants n=5 Participants	106 Participants n=4 Participants	325 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants	9 Participants n=4 Participants	37 Participants n=21 Participants
Region of Enrollment Puerto Rico	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment Romania	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment Hungary	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	23 Participants n=5 Participants	35 Participants n=7 Participants	13 Participants n=5 Participants	23 Participants n=4 Participants	94 Participants n=21 Participants
Region of Enrollment Japan	6 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants	39 Participants n=21 Participants
Region of Enrollment United Kingdom	8 Participants n=5 Participants	17 Participants n=7 Participants	8 Participants n=5 Participants	13 Participants n=4 Participants	46 Participants n=21 Participants
Region of Enrollment Spain	10 Participants n=5 Participants	21 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants	60 Participants n=21 Participants
Region of Enrollment Canada	6 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants	33 Participants n=21 Participants
Region of Enrollment South Korea	1 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Region of Enrollment Belgium	5 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	11 Participants n=21 Participants
Region of Enrollment Poland	6 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants	34 Participants n=21 Participants
Region of Enrollment France	4 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants	8 Participants n=4 Participants	33 Participants n=21 Participants
Region of Enrollment Australia	3 Participants n=5 Participants	13 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	30 Participants n=21 Participants
Region of Enrollment Germany	2 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants	24 Participants n=21 Participants
ADAS-Cog13 (13-item Alzheimer's Disease Assessment Scale)	27.9 Units on a Scale STANDARD_DEVIATION 8.3 • n=5 Participants	29.6 Units on a Scale STANDARD_DEVIATION 7.8 • n=7 Participants	27.0 Units on a Scale STANDARD_DEVIATION 7.5 • n=5 Participants	27.1 Units on a Scale STANDARD_DEVIATION 7.5 • n=4 Participants	27.9 Units on a Scale STANDARD_DEVIATION 7.8 • n=21 Participants

PRIMARY outcome

Timeframe: AZES Baseline through AZFD Week 26

Population: All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADAS-Cog13 measure. Feeder study AZES was stopped for futility, the original Delayed Start analysis was replaced with MMRM analysis and no comparisons between treatment groups were made.

ADAS-Cog13 (13-item version of ADAS-Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, apolipoprotein E4 (APOE4) status, acetylcholinesterase inhibitor (AChEI) use at baseline, age at baseline, and pooled country.

Outcome measures

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=139 Participants Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=75 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=131 Participants Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Change From Baseline Analysis on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)	9.61 Units on a scale Standard Error 1.60	9.25 Units on a scale Standard Error 1.21	8.41 Units on a scale Standard Error 1.65	10.41 Units on a scale Standard Error 1.25

SECONDARY outcome

Timeframe: AZES Baseline through AZFD Week 26

Population: All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADCS-iADL measure.

The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.

Outcome measures

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=139 Participants Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=74 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=129 Participants Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Change From Baseline Analysis on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL)	-9.19 Units on a scale Standard Error 1.47	-8.45 Units on a scale Standard Error 1.10	-7.37 Units on a scale Standard Error 1.51	-7.48 Units on a scale Standard Error 1.14

SECONDARY outcome

Timeframe: AZES Baseline through AZFD Week 26

Population: All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for FAQ score.

FAQ is a 10-item, caregiver-questionnaire and was administered to the study partner and asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now =1; Never did but could do now =0; Normal =0; Has difficulty but does by self =1; Requires assistance =2; Dependent =3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.

Outcome measures

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=137 Participants Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=74 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=130 Participants Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Change From Baseline on the Functional Activities Questionnaire (FAQ) Score	6.28 Units on a scale Standard Error 0.98	7.09 Units on a scale Standard Error 0.76	6.73 Units on a scale Standard Error 1.01	6.91 Units on a scale Standard Error 0.79

SECONDARY outcome

Timeframe: AZES Baseline through AZFD Week 26

Population: All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for iADRS.

The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.

Outcome measures

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=138 Participants Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=72 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=123 Participants Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score	-18.85 Units on a scale Standard Error 2.58	-17.57 Units on a scale Standard Error 1.97	-15.37 Units on a scale Standard Error 2.76	-18.37 Units on a scale Standard Error 2.09

SECONDARY outcome

Timeframe: AZES Baseline through AZFD Week 26

Population: All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for MMSE.

The MMSE is an instrument used to assess a participant's cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.

Outcome measures

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=139 Participants Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=75 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=131 Participants Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Change From Baseline on the Mini-Mental Status Examination (MMSE)	-5.84 Units on a scale Standard Error 0.71	-5.73 Units on a scale Standard Error 0.54	-4.72 Units on a scale Standard Error 0.72	-5.25 Units on a scale Standard Error 0.56

SECONDARY outcome

Timeframe: AZES Baseline through AZFD Week 52

Population: All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADAS-Cog13 measure.

ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.

Outcome measures

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=139 Participants Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=75 Participants Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=131 Participants Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Change From Baseline Analysis on the ADAS-Cog13	16.64 Units on a scale Standard Error 3.45	12.40 Units on a scale Standard Error 2.25	16.79 Units on a scale Standard Error 2.47	15.05 Units on a scale Standard Error 2.06

Adverse Events

AZES Placebo/AZFD Lanabecestat 20 mg

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg

Serious events: 8 serious events

Other events: 23 other events

Deaths: 0 deaths

AZES Placebo/AZFD Lanabecestat 50 mg

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg

Serious events: 7 serious events

Other events: 17 other events

Deaths: 1 deaths

Serious adverse events

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 participants at risk Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=139 participants at risk Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=74 participants at risk Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=131 participants at risk Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Cardiac disorders Bradycardia	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Gastrointestinal disorders Enteritis	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Gastrointestinal disorders Oesophageal motility disorder	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	1.4% 1/74 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Infections and infestations Diverticulitis	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	1.4% 1/74 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	1.3% 1/76 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Femoral neck fracture	1.3% 1/76 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Radiation proctitis	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	1.4% 1/74 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Investigations Electrocardiogram repolarisation abnormality	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	1.4% 1/74 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Investigations Weight decreased	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	1.3% 1/76 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Nervous system disorders Ischaemic stroke	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Nervous system disorders Optic neuritis	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Psychiatric disorders Depression	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.72% 1/139 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/131 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Psychiatric disorders Neuropsychiatric symptoms	0.00% 0/76 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/139 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	1.4% 1/74 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.76% 1/131 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.

Other adverse events

Measure	AZES Placebo/AZFD Lanabecestat 20 mg n=76 participants at risk Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg n=139 participants at risk Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD.	AZES Placebo/AZFD Lanabecestat 50 mg n=74 participants at risk Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.	AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg n=131 participants at risk Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
Gastrointestinal disorders Diarrhoea	2.6% 2/76 • Number of events 2 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	5.8% 8/139 • Number of events 8 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	2.7% 2/74 • Number of events 2 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	4.6% 6/131 • Number of events 6 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	1.3% 1/76 • Number of events 1 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	5.8% 8/139 • Number of events 10 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	4.1% 3/74 • Number of events 3 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	3.8% 5/131 • Number of events 7 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	5.3% 4/76 • Number of events 4 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	5.0% 7/139 • Number of events 8 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	4.1% 3/74 • Number of events 3 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	3.8% 5/131 • Number of events 8 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.
Psychiatric disorders Depression	5.3% 4/76 • Number of events 4 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	2.2% 3/139 • Number of events 3 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	0.00% 0/74 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.	1.5% 2/131 • Number of events 2 • Up To 156 Weeks All AZFD participants who received at least one dose of study drug.

Additional Information

AstraZeneca Information Center

AstraZeneca

Phone: 877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor shall review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. Investigator shall delay publication of their results of the study until the results of the multi-center study are published or presented, provided the multi-center results are published within 24 months of the termination.
• Publication restrictions are in place

Restriction type: OTHER